| First Author | Allen JD | Year | 2009 |
| Journal | Blood | Volume | 113 |
| Issue | 12 | Pages | 2695-705 |
| PubMed ID | 19124833 | Mgi Jnum | J:145444 |
| Mgi Id | MGI:3834742 | Doi | 10.1182/blood-2008-06-160861 |
| Citation | Allen JD, et al. (2009) P21-activated kinase regulates mast cell degranulation via effects on calcium mobilization and cytoskeletal dynamics. Blood 113(12):2695-705 |
| abstractText | Mast cells are key participants in allergic diseases via activation of high affinity IgE receptors (FcepsilonRI) resulting in release of pro-inflammatory mediators. The biochemical pathways linking IgE activation to calcium influx and cytoskeletal changes required for intracellular granule release are incompletely understood. We demonstrate, genetically, that Pak1 is required for this process. In a passive cutaneous anaphylaxis experiment, W(sh)/W(sh) mast cell-deficient mice locally reconstituted with Pak1(-/-) bone marrow-derived mast cells (BMMCs) experienced strikingly decreased allergen-induced vascular permeability as compared to controls. Consistent with the in vivo phenotype, Pak1(-/-) bone marrow-derived mast cells (BMMCs) exhibited a reduction in FcepsilonRI-induced degranulation. Further, Pak1(-/-) BMMCs demonstrated diminished calcium mobilization and altered depolymerization of cortical filamentous actin (F-actin) in response to FcepsilonRI stimulation. These data implicate Pak1 as an essential molecular target for modulating acute mast cell responses that contribute to allergic diseases. |
